Our overall goal is to understand the mechanisms by which pulmonary interstitial edema, the precursor to alveolar edema, affects pulmonary gas exchange. Pulmonary interstitial edema in the lung occurs as part of the transition between a healthy "dry" state, and a lung in which alveolar flooding is present. However, the early diagnosis of pulmonary interstitial edema is problematic. Our preliminary data show reversible changes in the inhomogeneity of pulmonary ventilation resulting from 1 hour of 30 degrees head-down tilt (HDT), accompanied by changes in the distribution of pulmonary perfusion, and by an increase in the total amount of water in the lungs determined from functional MRI studies of the lung. Such changes in both ventilation and perfusion have the potential to disrupt gas exchange in the lung. The evidence to date suggests that these changes result from alterations in lung fluid balance resulting from HDT. We propose a coordinated series of physiological, and functional imaging studies to test the hypothesis that the acute alterations in the fluid balance of the lung that result in pulmonary interstitial edema in humans will result in changes in ventilation-perfusion ratio, lung water content, gas mixing in the periphery of the lung, and pulmonary blood flow, and that these changes can be usefully characterized using the techniques we employ. Using a 30 degree head-down tilt model to rapidly provoke an acute increase in fluid content of the lung we will: 1) Measure alterations in the distribution of ventilation-perfusion ratio (VA/Q) in the lung using the multiple inert gas elimination technique, and using non-invasive measurements of intra-breath VA/Q. 2) Determine the relationship between alterations in ventilation distribution, pulmonary gas exchange and pulmonary mechanics as lung water is increased by 30 degree HDT. 3) Define and quantify the relationship between alterations in the heterogeneity of pulmonary blood flow and lung water content using functional magnetic resonance imaging (fMRI) and X-ray techniques. [unreadable] [unreadable] [unreadable]